Transdermal administrations of the active ingredients buprenorphine and fentanyl are the drug forms of choice for the treatment of chronic pain in long-term therapy. The continuous delivery of such highly active analgesics via the skin provides a continuous supply of a constant dose of analgesic to a patient with pain, thereby preventing plasma peaks and plasma troughs. This has the advantage that, by virtue of a low but sufficient plasma concentration of the active ingredient, there is occurrence neither of side effects due to overdose nor of avoidable states of pain due to undersupply. The skilled worker is aware, for example, of the commercial products TRANSTEC®, but also DUROGESIC® or DUROGESIC SMAT®, which have proven useful in the therapy of pain for some considerable time.
The disadvantage of the TTS in the therapy of pain, however, is that in order to maintain the so-called concentration gradient and hence the therapeutically desired plasma level of the active ingredient throughout the period of administration of the TTS it is always necessary for the store quantity of active ingredient present in the TTS to be greater than that actually delivered to the patient. A consequence of this is that worn TTS constitute a potential for abuse by, for example, those involved in the drugs scene. These groups of persons are perfectly capable of collecting worn TTS and extracting them with the most primitive of means in order to obtain the residual active ingredient still present and to consume it abusively in order to appease their drug addiction.
In the past, therefore, there has been no lack of attempts to prevent this unregulated misuse by advising patients to shred worn patches and then put them down the toilet into the sewerage system. A disadvantage of this method is that neither legislators nor drug manufacturers are able to guarantee that this recommendation is also reliably followed by the patients; moreover, mass disposal through the sewerage system constitutes an environmental problem which should not be underestimated.
Consequently, TTS were developed which as well as the active ingredient also contained an antagonist (e.g., WO 2004/098576 whose United States equivalent is U.S. Pat. No. 7,182,955; WO 90/04965 and WO 2004/037259 whose United States equivalent is United States Publication No. 2005/214223). The intention was to prevent, or at least significantly hinder, the above-described obtaining or abusive extraction of the active analgesic ingredient from used TTS. These protective measures, however, proved not to be enough to prevent medicament abuse, since it continues to be the case that the active ingredient itself can be separated from the antagonist by relatively simple means, by fractional precipitation.
WO 2007/137732 describes a TTS which in addition to an active ingredient further comprises an agent which is separate from the active ingredient, and which makes the active ingredient useless, in a solution. Additionally present to this end is a means which, following use of the TTS, allows the agent, therefore, to enter into contact with the active ingredient and make it useless. The disadvantage of this otherwise ideal solution, however, is that the agent in solution, on account of its high reactivity, restricts the shelf life, and that, in some cases, the risk exists of damage by liquid leakage in the course of transit as well.